Cytokine regulation of human sterol 12alpha-hydroxylase (CYP8B1) gene.

Cytokine regulation of human sterol 12alpha-hydroxylase (CYP8B1) gene.

Jahan Asmeen; Chiang John Y L

American journal of physiology. Gastrointestinal and liver physiology

2005

2005-04

Sterol 12alpha-hydroxylase (CYP8B1) catalyzes cholic acid synthesis in the liver and is feedback inhibited by bile acids. In addition to activating farnesoid X receptor (nuclear receptor subfamily 1H4), bile acids also induce inflammatory cytokines in hepatocytes. The objective of this study was to investigate the mechanism by which inflammatory cytokines inhibit human CYP8B1 gene transcription. Real-time PCR assays revealed that both chenodeoxycholic acid (CDCA) and interleukin-1beta (IL-1beta) markedly reduced CYP8B1, cholesterol 7alpha-hydroxylase CYP7A1 and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression levels in human primary hepatocytes. However, CDCA induced, but

Cell Line; Chenodeoxycholic Acid/pharmacology; Chromosome Mapping; DNA-Binding Proteins/genetics/metabolism; Enzyme Inhibitors/pharmacology; Gene Expression Regulation/*drug effects; Genetic/drug effects; Genetic/physiology; Hepatocyte Nuclear Factor 4; Hepatocytes/metabolism; Humans; Interleukin-1/*pharmacology; MAP Kinase Signaling System/drug effects/physiology; Messenger/antagonists & inhibitors; Mitogen-Activated Protein Kinase 8/metabolism; Mitogen-Activated Protein Kinases/antagonists & inhibitors; Phosphoproteins/genetics/metabolism; Phosphorylation; Promoter Regions; Response Elements/genetics; RNA; Steroid 12-alpha-Hydroxylase/antagonists & inhibitors/*genetics; Transcription; Transcription Factors/genetics/metabolism

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G685–695

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